Eighteen million Americans suffer from diabetes. Diabetes is a life-long disease marked by high concentrations of glucose in the blood. The sugar called glucose enters the bloodstream when food is digested. Glucose is a source of fuel for the body. In response to the glucose in the bloodstream, an organ called the pancreas makes the hormone insulin. The role of insulin is to move glucose from the bloodstream into muscle, fat, and liver cells, where it can be used as fuel. Individuals with diabetes either do not produce insulin (Type I diabetes) or are resistant to insulin (Type II diabetes). Consequently, the concentration of glucose in the blood in a person with diabetes may vary by a large amount dependent upon what they have eaten and the person's metabolic requirements.
There is no cure for diabetes. The goal of diabetes treatment is to stabilize the patient's blood-glucose concentration and eliminate the symptoms of high blood-glucose concentration. In order to control the patient's blood-glucose concentration, diabetics have to regularly monitor their blood-glucose concentration. If the patient's blood-glucose concentration is too high, they need an injection of insulin. If the patient's blood-glucose concentration is too low, they need to eat something with glucose in it. Blood-glucose concentration changes rapidly and the consequences of not controlling it properly can be immediate. A high concentration of glucose in the blood, termed hyperglycemia, can cause several problems including: frequent urination, excessive thirst, hunger, fatigue, weight loss, and blurry vision. A low concentration of glucose in the blood, termed hypoglycemia, can cause diabetic shock, coma and death. Poor blood-glucose concentration regulation also has long-term effects on health. Over the long-term, poor blood-glucose concentration regulation in diabetics can cause complications such as heart disease and kidney failure. Diabetes has high comorbidity with cardiac disease. Up to 45% of individuals with bradycardia or tachycardia also suffer from diabetes.
In order to reduce the risk of long-term complications from diabetes, the American Diabetes Association recommends that pre-meal blood-glucose concentrations fall in the range of 80 to 120 mg/dL and bedtime blood concentrations fall in the range of 100 to 140 mg/dL. Physicians also measure hemoglobin A1c (HbA1c) level. The HbA1c is a measure of average blood-glucose concentration during the previous two to three months. It is a useful way to monitor a patient's overall response to diabetes treatment over time. A person without diabetes has an HbA1c around 5%. People with diabetes should try to keep it below 7%. Studies have found dramatically lower rates of kidney, eye, and nervous system complications in patients with tight control of blood-glucose concentration. In addition, such control causes a significant drop in all diabetes-related deaths, including lower risks of heart attack and stroke.
Thus, it is important to keep a patient's blood-glucose concentration near normal concentrations. However, with blood-glucose kept at near normal concentrations, diabetics are at higher risk of hypoglycemia as the glucose becomes depleted over time. Blood-glucose concentration monitoring is the critical first step that allows diabetics to control their blood-glucose concentration. Typically, a sample of blood must be drawn and then the blood-glucose concentration assayed using color changing strips or an electrical device. To ensure proper dosage of insulin, individuals with diabetes use lancets to draw blood for conventional glucose measurements. A disadvantage of current blood-glucose concentration testing is that the painful process of drawing blood limits the number of times an individual is willing to take measurements. It is also a disadvantage that the process requires active user intervention.
A method for external monitoring of blood-glucose concentration without drawing blood is disclosed in a publication by Cho et al., entitled “Noninvasive Measurement of Glucose by Metabolic Heat Conformation Method,” Clinical Chemistry 50:10 1894-1898 (2004), which is incorporated herein by reference. This publication utilizes a metabolic heat conformation method which depends upon measuring body surface temperature and conductive and radiative heat losses from the subject. These heat losses are tied through the circulatory system to glucose metabolism, which is the primary source of heat generation in the body. Using analysis of the surface temperature measurements and external peripheral measurements of blood flow, hematocrit and oxygen saturation, and standard blood-glucose concentration measurements, the authors developed relationships between the external measurements that predicted measured blood-glucose concentration. The MHC method utilizes precise measurements of external heat loss to estimate the rate of glucose metabolism and then correlates that to the blood-glucose concentration. However, while the method disclosed by Cho et al. has the advantage that it does not require blood to be drawn, it still requires active user intervention. See, also, U.S. Pat. No. 5,795,305 entitled “Process And Device For Non-Invasive Determination Of blood-glucose concentration In Parts Of The Human Body” to Cho et al.; and U.S. Pat. No. 5,924,996 titled “Process And Device For Detecting The Exchange Of Heat Between The Human Body And The Invented Device And Its Correlation To The blood-glucose concentration In Human Blood” to Cho et al. both of which are incorporated herein by reference. Moreover, the method disclosed by Cho, because it requires external measurements of the heat lost at the surface of the human body, cannot be utilized in an implantable device.
In view of the many disadvantages of conventional external blood-glucose concentration monitoring techniques, implantable blood-glucose concentration monitors have been developed, which include sensors for mounting directly within the blood stream. Most implantable glucose sensors are amperometric enzymatic biosensors which use immobilized glucose oxidase, an enzyme that catalyzes the oxidation of glucose to gluconic acid with the production of hydrogen peroxide. However, such amperometric enzymatic biosensors tend to clog very quickly. Thus, an implantable device that would continually and reliably measure blood-glucose concentration without requiring amperometric enzymatic biosensors would be very desirable. Moreover, as with any implantable device, there are attended risks associated with implanting the blood-glucose concentration monitor, such as adverse reactions to anesthetics employed during the implantation procedure or the onset of subsequent infections. Hence, it would be desirable to provide for automatic blood-glucose concentration monitoring using medical devices that would otherwise need to be implanted anyway, to thereby minimize the risks associated with the implantation of additional devices.
In view of the disadvantages of the state of the art with respect to glucose monitoring, it would be desirable to have a system that could painlessly measure blood-glucose concentration without drawing blood each time.
It would also be desirable to have a system that would automatically measure blood-glucose concentration of a patient without active user intervention.
It would further be desirable to have a system that would warn a diabetic before their blood-glucose concentration fell too low.
It would still further be desirable to have a system that could warn others if the diabetic's blood-glucose concentration fell low enough that they might be in diabetic shock.
It would yet further be desirable to have a system that could control delivery of insulin to a diabetic to better regulate their blood-glucose concentration.
It would yet further be desirable to have an implantable system that could measure glucose concentration without amperometric enzymatic biosensors.